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The survival with unsuspected GBC was related to stage and it was confirmed that a carefully performed LC is adequate treatment for Stage 1A and B cancer. The LC procedure does not adversely affect the prognosis of unsuspected GBC, regardless of whether it is detected during or after LC.

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), are autosomal recessive diseases caused by deficiency of peroxisome assembly as well as malfunction of peroxisomes, where >10 genotypes have been reported. ZS patients manifest the most severe clinical and biochemical abnormalities, while those with NALD and IRD show the least severity and the mildest features, respectively. PEX1 is the causative gene for PBDs of complementation group I (CG1), the highest incidence PBD, and encodes the peroxin, Pex1p, a member of the AAA ATPase family. In the present work, we found that peroxisomes were morphologically and biochemically formed at 30 but not 37 degrees C, in the fibroblasts from all CG1 IRD patients examined, whereas almost no peroxisomes were seen in ZS and NALD cells, even at 30 degrees C. A point missense mutation, G843D, was identified in the PEX1 allele of most CG1 IRD patients. The mutant PEX1, termed HsPEX1G843D, gave rise to the same temperature-sensitive phenotype on CG1 CHO cell mutants upon transfection. Collectively, these results demonstrate temperature-sensitive peroxisome assembly to be responsible for the mildness of the clinical features of PEX1 -defective IRD of CG1.

The prognosis after surgical resection of pancreatic carcinoma mostly depends on tumor factors. In this study, it was difficult to identify the determinants of long-term survival in patients with resectable tumors.

Few data exists regarding the clinical impact of breastfeeding in infantile sitosterolaemic cases. We report four Japanese infantile cases of sitosterolaemia, an extremely rare inherited disease characterised by increased serum levels of plant sitosterol, presenting with severe hypercholesterolaemia and systemic xanthomas exacerbated by breastfeeding. In these four cases, genetic analyses were performed for low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor adaptor protein 1 and ATP-binding cassette (ABC) subfamily G member 5 and 8 (ABCG5 and ABCG8) genes. We assessed their clinical manifestations, including responsiveness to a variety of treatments, especially to weaning from breastfeeding and use of ezetimibe. Two pairs of mutations in the ABCG5 gene in each case, including two novel mutations (c.130C>T or p.Ser44Ala and c.1813_1817delCTTTT or p.Pro558GlufsX14) and two known mutations (c.1306G>A or p.Arg389His and c.1336C>T or p.Arg446X), were identified. Significant reductions in cholesterol levels were obtained by means of weaning from breastfeeding alone. Substantial reductions in sitosterol levels, without any apparent side effects, were observed with ezetimibe. In conclusion, we have identified infantile Japanese sitosterolaemic subjects with extreme hypercholesterolaemia exacerbated by breastfeeding. Their unique response to weaning from breastfeeding, as well as to use of ezetimibe, could provide insights into the metabolic basis of sterols in humans.

Peroxisome biogenesis disorders, including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease, are lethal hereditary diseases caused by abnormalities in peroxisomal assembly. To date, 12 genotypes have been identified. We now have evidence that the complete human cDNA encoding Pex13p, an SH3 protein of a docking factor for the peroxisome targeting signal 1 receptor (Pex5p), rescues peroxisomal matrix protein import and its assembly in fibroblasts from PBD patients of complementation group H. In addition, we detected mutations on the human PEX13 cDNA in two patients of group H. A severe phenotype of a ZS patient (H-02) was homozygous for a nonsense mutation, W234ter, which results in the loss of not only the SH3 domain but also the putative transmembrane domain of Pex13p. A more mildly affected NALD patient (H-01), whose fibroblasts showed the temperature-sensitive (TS) phenotype, was homozygous for a missense mutation in the SH3 domain of Pex13p, I326T. This mutant PEX13 cDNA expression in a PEX13-defective CHO mutant showed I326T to be a TS mutation and thus suggested that Pex13p with the I326T mutation in the SH3 domain is stable at 30 degrees C but is somewhat unstable at 37 degrees C.

Summary:Purpose: To evaluate antibody-mediated and cytotoxic T cell-mediated pathogenicity that has been implicated as the autoimmune pathophysiological mechanism in Rasmussen's encephalitis.Methods: We examined autoantibodies against the N-methyl-

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